This application relates to signal transduction proteins.
The epidermal growth factor receptor (EGF-R) is a transmembrane glycoprotein with an extracellular ligand binding domain and a cytoplasmic tyrosine kinase domain Ullrich et al., Cell 61, 203 (1990); Schlessinger et al., Neuron 9, 383 (1992)!. Treatment of cells with epidermal growth factor (EGF) causes increased EGF receptor tyrosine kinase activity, i.e., the activated state. Substrates for the activated EGF-R tyrosine kinase include the COOH terminal region of the receptor Ullrich et al., supra; Schlessinger et al., supra!. The tyrosine phosphorylated EGF receptor binds to modular signaling proteins that contain Src homolog (SH2) or PTB domains Ullrich et al., supra; Schlessinger et al., supra; Koch et al, Science 252, 668 (1991); Pawson et al., Cell 71, 359 (1992); Kavanaugh et al., Science 266, 1862 (1994); Bork et al., Cell 80, 693 (1995); Kavanaugh et al., Science 268, 1177 (1995)!. However, prior to the formation of the receptor SH2/PTB signaling complex, the non-activated EGF receptor is proposed to interact with other proteins Ullrich et al., supra; Schlessinger et al., supra!. The identity of proteins within the non-activated EGF-R complex is currently unknown.